Stem cells (SC) play a crucial role in tissue morphogenesis during development and in physiological renewal throughout adulthood. They are also vital for adult tissue regeneration after injuries. The mammary gland and prostate contain basal and luminal cells that maintain their lineages under physiological conditions. Mutations promoting cancer development and regenerative stimuli enhance the differentiation potential of stem cells. However, the underlying molecular mechanisms facilitating this stem cell fate expansion remain poorly understood.
In a study published in Nature Communications, researchers led by Professor Cédric Blanpain, MD/PhD, an investigator at the WEL Research Institute, Director of the Stem Cells and Cancer Laboratory, and Professor at the Université libre de Bruxelles, discovered that collagen signaling and extracellular matrix stiffness control stem cell fate.
Utilizing multidisciplinary approaches that combined stem cell behavior analysis, organoid culture, single-cell sequencing, and functional experiments, Chen Jiang and colleagues investigated how collagen signaling and matrix stiffness regulate stem cell fate.
By establishing a molecular profile of stem cells under varying stiffness and collagen abundance conditions, the researchers identified a specific collagen signaling cascade as a regulator of stem cell fate. Pharmacological blockade or genetic inactivation of components in this signaling cascade decreased the ability of basal cells to differentiate into luminal cells. "It was fascinating to discover that collagen signaling is a common mechanism controlling stem cell fate across different tissues such as the mammary gland and prostate," stated Dr. Chen Jiang, the first author of the article.
"Our findings reveal a conserved mechanism by which the composition and stiffness of the extracellular environment regulate the fate of mammary and prostate stem cells, providing key insights into how stem cell fate is regulated by matrix composition. It will be important to define how these mechanisms contribute to tissue regeneration, tumor initiation, and progression. Targeting collagen signaling could be crucial for hindering tumor development," commented Cédric Blanpain, the director of this study.